NO864126L - Fremgangsmaate for fremstilling av terapeutisk aktive pyridon-derivater. - Google Patents
Fremgangsmaate for fremstilling av terapeutisk aktive pyridon-derivater.Info
- Publication number
- NO864126L NO864126L NO864126A NO864126A NO864126L NO 864126 L NO864126 L NO 864126L NO 864126 A NO864126 A NO 864126A NO 864126 A NO864126 A NO 864126A NO 864126 L NO864126 L NO 864126L
- Authority
- NO
- Norway
- Prior art keywords
- compound
- formula
- dihydropyridin
- oxo
- hydrogen
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 51
- 238000000034 method Methods 0.000 title claims description 24
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical class OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 title description 3
- 230000001225 therapeutic effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 209
- 239000001257 hydrogen Substances 0.000 claims description 48
- 229910052739 hydrogen Inorganic materials 0.000 claims description 48
- 238000006243 chemical reaction Methods 0.000 claims description 44
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 43
- 150000003839 salts Chemical class 0.000 claims description 32
- 239000000126 substance Substances 0.000 claims description 29
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 27
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
- CVQUWLDCFXOXEN-UHFFFAOYSA-N Pyran-4-one Chemical compound O=C1C=COC=C1 CVQUWLDCFXOXEN-UHFFFAOYSA-N 0.000 claims description 27
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 27
- 150000002431 hydrogen Chemical class 0.000 claims description 20
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 19
- 229910052760 oxygen Inorganic materials 0.000 claims description 19
- 239000001301 oxygen Substances 0.000 claims description 19
- -1 amino, hydroxy Chemical group 0.000 claims description 18
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 18
- 229910052717 sulfur Inorganic materials 0.000 claims description 17
- 239000011593 sulfur Substances 0.000 claims description 17
- 229910052731 fluorine Inorganic materials 0.000 claims description 13
- 239000011737 fluorine Substances 0.000 claims description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 13
- GCNTZFIIOFTKIY-UHFFFAOYSA-N 4-hydroxypyridine Chemical compound OC1=CC=NC=C1 GCNTZFIIOFTKIY-UHFFFAOYSA-N 0.000 claims description 11
- 239000005864 Sulphur Substances 0.000 claims description 10
- 125000001153 fluoro group Chemical group F* 0.000 claims description 10
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 claims description 10
- 230000007062 hydrolysis Effects 0.000 claims description 10
- 238000006460 hydrolysis reaction Methods 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- GDMRFHZLKNYRRO-UHFFFAOYSA-N 3-(4-aminophenyl)-4-methyl-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(N)C=C1 GDMRFHZLKNYRRO-UHFFFAOYSA-N 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- OOTPDLYEDHRWNL-UHFFFAOYSA-N 4-methyl-3-[4-(4-oxopyridin-1-yl)phenyl]-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(N2C=CC(=O)C=C2)C=C1 OOTPDLYEDHRWNL-UHFFFAOYSA-N 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 6
- 238000007363 ring formation reaction Methods 0.000 claims description 6
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 5
- 238000006798 ring closing metathesis reaction Methods 0.000 claims description 5
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims description 4
- 230000018044 dehydration Effects 0.000 claims description 4
- 238000006297 dehydration reaction Methods 0.000 claims description 4
- YRKHTLAHNUQIEB-UHFFFAOYSA-N 2-[4-(4-oxopyridin-1-yl)phenyl]-4h-1,3,4-oxadiazin-5-one Chemical compound N1C(=O)COC(C=2C=CC(=CC=2)N2C=CC(=O)C=C2)=N1 YRKHTLAHNUQIEB-UHFFFAOYSA-N 0.000 claims description 3
- ZSEXHZFLSFGGGD-UHFFFAOYSA-N 3-[4-(4-oxopyridin-1-yl)phenyl]-1h-pyridazin-6-one Chemical compound C1=CC(=O)C=CN1C1=CC=C(C2=NNC(=O)C=C2)C=C1 ZSEXHZFLSFGGGD-UHFFFAOYSA-N 0.000 claims description 3
- YFJSHOLVVVAWFQ-UHFFFAOYSA-N 3-[4-(4-oxopyridin-1-yl)phenyl]-4,5-dihydro-1h-pyridazin-6-one Chemical compound N1C(=O)CCC(C=2C=CC(=CC=2)N2C=CC(=O)C=C2)=N1 YFJSHOLVVVAWFQ-UHFFFAOYSA-N 0.000 claims description 3
- ONWLPJCCIDKQLY-UHFFFAOYSA-N 3-methyl-4-oxo-4-[4-(4-oxopyridin-1-yl)phenyl]butanoic acid Chemical compound C1=CC(C(=O)C(CC(O)=O)C)=CC=C1N1C=CC(=O)C=C1 ONWLPJCCIDKQLY-UHFFFAOYSA-N 0.000 claims description 3
- YDNGAMGIZWLQJD-UHFFFAOYSA-N 5-[4-(4-oxopyridin-1-yl)phenyl]-1h-pyrazin-2-one Chemical compound C1=CC(=O)C=CN1C1=CC=C(C=2N=CC(=O)NC=2)C=C1 YDNGAMGIZWLQJD-UHFFFAOYSA-N 0.000 claims description 3
- JSOPJCADTSTYGF-UHFFFAOYSA-N 5-[4-(4-oxopyridin-1-yl)phenyl]-3h-1,3,4-oxadiazol-2-one Chemical compound O1C(=O)NN=C1C1=CC=C(N2C=CC(=O)C=C2)C=C1 JSOPJCADTSTYGF-UHFFFAOYSA-N 0.000 claims description 3
- XSQVNNTYPPOQQR-UHFFFAOYSA-N 5-[4-(4-oxopyridin-1-yl)phenyl]-3h-1,3,4-thiadiazol-2-one Chemical compound S1C(=O)NN=C1C1=CC=C(N2C=CC(=O)C=C2)C=C1 XSQVNNTYPPOQQR-UHFFFAOYSA-N 0.000 claims description 3
- JXASVHNWTXHVPC-UHFFFAOYSA-N 6-[4-(4-oxopyridin-1-yl)phenyl]-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound N1C(=O)NCC(C=2C=CC(=CC=2)N2C=CC(=O)C=C2)=N1 JXASVHNWTXHVPC-UHFFFAOYSA-N 0.000 claims description 3
- JJDDYOOKJOPYHZ-UHFFFAOYSA-N 7-(4-oxopyridin-1-yl)-2,5-dihydroindeno[1,2-c]pyridazin-3-one Chemical compound C1=CC(=O)C=CN1C1=CC=C2C3=NNC(=O)C=C3CC2=C1 JJDDYOOKJOPYHZ-UHFFFAOYSA-N 0.000 claims description 3
- FYOOPTOTTWKBBJ-UHFFFAOYSA-N 8-(4-oxopyridin-1-yl)-4,4a,5,6-tetrahydro-2h-benzo[h]cinnolin-3-one Chemical compound C=1C=C2C3=NNC(=O)CC3CCC2=CC=1N1C=CC(=O)C=C1 FYOOPTOTTWKBBJ-UHFFFAOYSA-N 0.000 claims description 3
- 238000006356 dehydrogenation reaction Methods 0.000 claims description 3
- 150000003385 sodium Chemical class 0.000 claims description 3
- OOTPDLYEDHRWNL-LLVKDONJSA-N (4r)-4-methyl-3-[4-(4-oxopyridin-1-yl)phenyl]-4,5-dihydro-1h-pyridazin-6-one Chemical compound C[C@@H]1CC(=O)NN=C1C1=CC=C(N2C=CC(=O)C=C2)C=C1 OOTPDLYEDHRWNL-LLVKDONJSA-N 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- COLXVKXCOPCHGX-UHFFFAOYSA-N 2-[4-(4-oxopyridin-1-yl)phenyl]-4h-1,3,4-thiadiazin-5-one Chemical compound N1C(=O)CSC(C=2C=CC(=CC=2)N2C=CC(=O)C=C2)=N1 COLXVKXCOPCHGX-UHFFFAOYSA-N 0.000 claims description 2
- OYKRWJFUYGBWTO-UHFFFAOYSA-N 5-methyl-6-[4-(4-oxopyridin-1-yl)phenyl]-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound CC1NC(=O)NN=C1C1=CC=C(N2C=CC(=O)C=C2)C=C1 OYKRWJFUYGBWTO-UHFFFAOYSA-N 0.000 claims description 2
- XYLFHMSBUDSHPI-UHFFFAOYSA-N 6-methyl-5-[4-(4-oxopyridin-1-yl)phenyl]-3,6-dihydro-1,3,4-thiadiazin-2-one Chemical compound CC1SC(=O)NN=C1C1=CC=C(N2C=CC(=O)C=C2)C=C1 XYLFHMSBUDSHPI-UHFFFAOYSA-N 0.000 claims description 2
- GDMRFHZLKNYRRO-SSDOTTSWSA-N OR-1855 Chemical compound C[C@@H]1CC(=O)NN=C1C1=CC=C(N)C=C1 GDMRFHZLKNYRRO-SSDOTTSWSA-N 0.000 claims description 2
- 238000006114 decarboxylation reaction Methods 0.000 claims description 2
- 101100277337 Arabidopsis thaliana DDM1 gene Proteins 0.000 claims 1
- 101150113676 chr1 gene Proteins 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 63
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 239000007787 solid Substances 0.000 description 27
- 238000010992 reflux Methods 0.000 description 26
- 239000000243 solution Substances 0.000 description 25
- 239000000203 mixture Substances 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- 239000002585 base Substances 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 229960000583 acetic acid Drugs 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 12
- 239000002904 solvent Substances 0.000 description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- 239000012258 stirred mixture Substances 0.000 description 9
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 8
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
- 229910052794 bromium Inorganic materials 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- 238000001953 recrystallisation Methods 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- 239000012312 sodium hydride Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 210000004623 platelet-rich plasma Anatomy 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 5
- 241000282326 Felis catus Species 0.000 description 5
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 229940095074 cyclic amp Drugs 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 239000000825 pharmaceutical preparation Substances 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- KOAXIIOHPXRHHO-UHFFFAOYSA-N 1,5-bis(dimethylamino)penta-1,4-dien-3-one Chemical compound CN(C)C=CC(=O)C=CN(C)C KOAXIIOHPXRHHO-UHFFFAOYSA-N 0.000 description 4
- PBAYDYUZOSNJGU-UHFFFAOYSA-N Chelidonic acid Chemical compound OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 239000000010 aprotic solvent Substances 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 229960001340 histamine Drugs 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 229940124549 vasodilator Drugs 0.000 description 4
- 239000003071 vasodilator agent Substances 0.000 description 4
- 230000002861 ventricular Effects 0.000 description 4
- HQQULPUXSRHOGE-UHFFFAOYSA-N 1,4-Pentadiyn-3-one Chemical compound C#CC(=O)C#C HQQULPUXSRHOGE-UHFFFAOYSA-N 0.000 description 3
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 102000000584 Calmodulin Human genes 0.000 description 3
- 108010041952 Calmodulin Proteins 0.000 description 3
- 206010007559 Cardiac failure congestive Diseases 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 206010019280 Heart failures Diseases 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 230000000747 cardiac effect Effects 0.000 description 3
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 238000007429 general method Methods 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 230000004936 stimulating effect Effects 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- HUTNOYOBQPAKIA-UHFFFAOYSA-N 1h-pyrazin-2-one Chemical group OC1=CN=CC=N1 HUTNOYOBQPAKIA-UHFFFAOYSA-N 0.000 description 2
- IHPYMWDTONKSCO-UHFFFAOYSA-N 2,2'-piperazine-1,4-diylbisethanesulfonic acid Chemical compound OS(=O)(=O)CCN1CCN(CCS(O)(=O)=O)CC1 IHPYMWDTONKSCO-UHFFFAOYSA-N 0.000 description 2
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- AGQLOTJUTCKLOE-UHFFFAOYSA-N 2-chloro-1-(4-fluorophenyl)propan-1-one Chemical compound CC(Cl)C(=O)C1=CC=C(F)C=C1 AGQLOTJUTCKLOE-UHFFFAOYSA-N 0.000 description 2
- RYMQQZNEVWFEFA-UHFFFAOYSA-N 3,4-dihydro-1,3,4-thiadiazin-2-one Chemical compound O=C1NNC=CS1 RYMQQZNEVWFEFA-UHFFFAOYSA-N 0.000 description 2
- PPYCUIIWIHCVPL-UHFFFAOYSA-N 4-(4-fluorophenyl)-3-methyl-4-oxobutanoic acid Chemical compound OC(=O)CC(C)C(=O)C1=CC=C(F)C=C1 PPYCUIIWIHCVPL-UHFFFAOYSA-N 0.000 description 2
- FEPVFNALOJTRJT-UHFFFAOYSA-N 4-(4-oxopyridin-1-yl)benzaldehyde Chemical compound C1=CC(C=O)=CC=C1N1C=CC(=O)C=C1 FEPVFNALOJTRJT-UHFFFAOYSA-N 0.000 description 2
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
- FKZXYJYTUSGIQE-UHFFFAOYSA-N 4-nitrobenzohydrazide Chemical compound NNC(=O)C1=CC=C([N+]([O-])=O)C=C1 FKZXYJYTUSGIQE-UHFFFAOYSA-N 0.000 description 2
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB858525654A GB8525654D0 (en) | 1985-10-17 | 1985-10-17 | Chemical compounds |
| GB868601667A GB8601667D0 (en) | 1986-01-23 | 1986-01-23 | Chemical compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO864126D0 NO864126D0 (no) | 1986-10-16 |
| NO864126L true NO864126L (no) | 1987-04-21 |
Family
ID=26289898
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO864126A NO864126L (no) | 1985-10-17 | 1986-10-16 | Fremgangsmaate for fremstilling av terapeutisk aktive pyridon-derivater. |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US4906628A (xx) |
| EP (1) | EP0220044B1 (xx) |
| CN (1) | CN1009092B (xx) |
| AU (1) | AU586042B2 (xx) |
| DE (1) | DE3677316D1 (xx) |
| DK (1) | DK491186A (xx) |
| ES (1) | ES2031821T3 (xx) |
| FI (1) | FI864193A7 (xx) |
| GR (1) | GR3001555T3 (xx) |
| HU (1) | HU196788B (xx) |
| IL (1) | IL80296A (xx) |
| NO (1) | NO864126L (xx) |
| NZ (1) | NZ217931A (xx) |
| PH (1) | PH22428A (xx) |
| PT (1) | PT83530B (xx) |
| ZW (1) | ZW20586A1 (xx) |
Families Citing this family (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4962110A (en) * | 1985-03-12 | 1990-10-09 | Smith Kline & French Laboratories Limited | Pyridazinone derivatives |
| GB8610369D0 (en) * | 1986-04-28 | 1986-06-04 | Smith Kline French Lab | Heterocyclic compounds |
| GB8621864D0 (en) * | 1986-09-11 | 1986-10-15 | Smith Kline French Lab | Chemical process |
| GB8901836D0 (en) * | 1989-01-27 | 1989-03-15 | Sobio Lab | Compounds |
| DE3913597A1 (de) * | 1989-04-25 | 1990-11-08 | Heumann Pharma Gmbh & Co | Diazinderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| DK0482208T3 (da) * | 1990-04-25 | 2000-09-18 | Nissan Chemical Ind Ltd | Pyridazinonderivat |
| ES2131506T3 (es) * | 1990-09-21 | 1999-08-01 | Rohm & Haas | Dihidropiridacinonas y piridacinonas como fungicidas. |
| CN1038249C (zh) * | 1991-08-28 | 1998-05-06 | 罗姆和哈斯公司 | 含有二氢哒嗪酮及其相关化合物的杀菌组合物 |
| US5958926A (en) * | 1996-11-01 | 1999-09-28 | Nitromed, Inc. | Nitrosated and nitrosylated phosphodiesterase inhibitor compounds, compositions and their uses |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| DE102004011512B4 (de) | 2004-03-08 | 2022-01-13 | Boehringer Ingelheim Vetmedica Gmbh | Pharmazeutische Zubereitung enthaltend Pimobendan |
| US8980894B2 (en) | 2004-03-25 | 2015-03-17 | Boehringer Ingelheim Vetmedica Gmbh | Use of PDE III inhibitors for the treatment of asymptomatic (occult) heart failure |
| EP1579862A1 (en) * | 2004-03-25 | 2005-09-28 | Boehringer Ingelheim Vetmedica Gmbh | Use of PDE III inhibitors for the reduction of heart size in mammals suffering from heart failure |
| EP2258359A3 (en) | 2005-08-26 | 2011-04-06 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation with sabcomelin |
| CA2620333A1 (en) | 2005-08-26 | 2007-03-01 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation |
| AU2006304787A1 (en) | 2005-10-21 | 2007-04-26 | Braincells, Inc. | Modulation of neurogenesis by PDE inhibition |
| EP2314289A1 (en) | 2005-10-31 | 2011-04-27 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
| KR20080065704A (ko) | 2005-11-09 | 2008-07-14 | 콤비네이토릭스, 인코포레이티드 | 의학적 이상의 치료 방법들, 조성물들, 및 키트들 |
| JP5312034B2 (ja) * | 2005-11-14 | 2013-10-09 | ベーリンガー インゲルハイム フェトメディカ ゲゼルシャフト ミット ベシュレンクテル ハフツング | 無症候性（潜在性）心不全の治療のためのｐｄｅｉｉｉ阻害剤の使用 |
| US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| WO2007104035A1 (en) * | 2006-03-08 | 2007-09-13 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| US20100009983A1 (en) * | 2006-05-09 | 2010-01-14 | Braincells, Inc. | 5 ht receptor mediated neurogenesis |
| JP2009536667A (ja) | 2006-05-09 | 2009-10-15 | ブレインセルス，インコーポレイティド | ５ｈｔ受容体介在性の神経新生 |
| EP2021000A2 (en) | 2006-05-09 | 2009-02-11 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
| MX2009002496A (es) * | 2006-09-08 | 2009-07-10 | Braincells Inc | Combinaciones que contienen un derivado de 4-acilaminopiridina. |
| US20080103165A1 (en) * | 2006-09-19 | 2008-05-01 | Braincells, Inc. | Ppar mediated modulation of neurogenesis |
| US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
| EP1920785A1 (en) * | 2006-11-07 | 2008-05-14 | Boehringer Ingelheim Vetmedica Gmbh | Liquid preparation comprising a complex of pimobendan and cyclodextrin |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| EP2170930B3 (en) | 2007-06-04 | 2013-10-02 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| JP2011522828A (ja) | 2008-06-04 | 2011-08-04 | シナジー ファーマシューティカルズ インコーポレイテッド | 胃腸障害、炎症、癌、およびその他の障害の治療のために有用なグアニル酸シクラーゼのアゴニスト |
| EP2321341B1 (en) | 2008-07-16 | 2017-02-22 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
| CA2744505A1 (en) | 2008-11-25 | 2010-06-03 | Boehringer Ingelheim Vetmedica Gmbh | Phosphodiesterase type iii (pde iii) inhibitors or ca2+-sensitizing agents for the treatment of hypertrophic cardiomyopathy |
| US20100216805A1 (en) | 2009-02-25 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| CN103764672A (zh) | 2011-03-01 | 2014-04-30 | 辛纳吉制药公司 | 制备鸟苷酸环化酶c激动剂的方法 |
| WO2013106547A1 (en) | 2012-01-10 | 2013-07-18 | President And Fellows Of Harvard College | Beta-cell replication promoting compounds and methods of their use |
| WO2013135852A1 (en) | 2012-03-15 | 2013-09-19 | Boehringer Ingelheim Vetmedica Gmbh | Pharmaceutical tablet formulation for the veterinary medical sector, method of production and use thereof |
| US9545446B2 (en) | 2013-02-25 | 2017-01-17 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase and their uses |
| CA2905435A1 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Compositions useful for the treatment of gastrointestinal disorders |
| US9708367B2 (en) | 2013-03-15 | 2017-07-18 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase and their uses |
| RS65632B1 (sr) | 2013-06-05 | 2024-07-31 | Bausch Health Ireland Ltd | Ultra-prečišćeni agonisti guanilat-ciklaze c, postupak njihove pripreme i upotrebe |
| CA2915445C (en) | 2013-07-19 | 2024-04-23 | Boehringer Ingelheim Vetmedica Gmbh | Preserved etherified cyclodextrin derivatives containing liquid aqueous pharmaceutical composition |
| CN114404588A (zh) | 2013-08-09 | 2022-04-29 | 阿德利克斯公司 | 用于抑制磷酸盐转运的化合物和方法 |
| EA201992230A1 (ru) | 2013-12-04 | 2020-02-28 | Бёрингер Ингельхайм Ветмедика Гмбх | Улучшенные фармацевтические композиции пимобендана |
| US10537570B2 (en) | 2016-04-06 | 2020-01-21 | Boehringer Ingelheim Vetmedica Gmbh | Use of pimobendan for the reduction of heart size and/or the delay of onset of clinical symptoms in patients with asymptomatic heart failure due to mitral valve disease |
| JOP20200024A1 (ar) | 2017-08-04 | 2020-02-02 | Bayer Ag | مركبات ثنائي هيدروكساديازينون |
| EP3661917B1 (en) | 2017-08-04 | 2022-05-11 | Bayer Aktiengesellschaft | 6-((3-trifluoromethyl)phenyl)-4,5-dihydropyridazin-3(2h)-one derivatives as pde3a and pde3b inhibitors for treating cancer |
| TWI750573B (zh) | 2019-02-01 | 2021-12-21 | 德商拜耳廠股份有限公司 | 1,2,4-三-3(2h)-酮化合物 |
| WO2020237096A1 (en) | 2019-05-21 | 2020-11-26 | Ardelyx, Inc. | Combination for lowering serum phosphate in a patient |
| DE102021105255B4 (de) * | 2021-03-04 | 2022-10-13 | Festo Se & Co. Kg | Vorrichtung mit über eine Verbindungsschnittstelle verbundenen Bauteilen und Verfahren zur Verbindung von Bauteilen |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL69407A (en) * | 1982-08-23 | 1987-10-20 | Warner Lambert Co | 2(1h)-pyridinones,their preparation and pharmaceutical compositions containing them |
| DE3600891A1 (de) * | 1986-01-15 | 1987-07-16 | Bayer Ag | 1,8-verbrueckte 4-chinolon-3-carbonsaeuren und diese enthaltende arzneimittel |
-
1986
- 1986-10-13 DE DE8686307911T patent/DE3677316D1/de not_active Expired - Lifetime
- 1986-10-13 ES ES198686307911T patent/ES2031821T3/es not_active Expired - Lifetime
- 1986-10-13 EP EP86307911A patent/EP0220044B1/en not_active Expired - Lifetime
- 1986-10-13 ZW ZW205/86A patent/ZW20586A1/xx unknown
- 1986-10-13 PT PT83530A patent/PT83530B/pt not_active IP Right Cessation
- 1986-10-14 IL IL80296A patent/IL80296A/xx unknown
- 1986-10-14 US US06/918,425 patent/US4906628A/en not_active Expired - Lifetime
- 1986-10-14 PH PH34365A patent/PH22428A/en unknown
- 1986-10-14 DK DK491186A patent/DK491186A/da not_active Application Discontinuation
- 1986-10-15 NZ NZ217931A patent/NZ217931A/xx unknown
- 1986-10-16 AU AU64166/86A patent/AU586042B2/en not_active Ceased
- 1986-10-16 NO NO864126A patent/NO864126L/no unknown
- 1986-10-16 FI FI864193A patent/FI864193A7/fi not_active IP Right Cessation
- 1986-10-16 HU HU864319A patent/HU196788B/hu not_active IP Right Cessation
- 1986-10-16 CN CN86106546A patent/CN1009092B/zh not_active Expired
-
1989
- 1989-12-18 US US07/452,072 patent/US5066653A/en not_active Expired - Lifetime
-
1991
- 1991-03-05 GR GR91400270T patent/GR3001555T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN86106546A (zh) | 1987-05-20 |
| DE3677316D1 (de) | 1991-03-07 |
| US4906628A (en) | 1990-03-06 |
| EP0220044A3 (en) | 1988-02-24 |
| HU196788B (en) | 1989-01-30 |
| NO864126D0 (no) | 1986-10-16 |
| PT83530B (pt) | 1989-05-31 |
| AU6416686A (en) | 1987-04-30 |
| ZW20586A1 (en) | 1988-05-25 |
| US5066653A (en) | 1991-11-19 |
| AU586042B2 (en) | 1989-06-29 |
| PH22428A (en) | 1988-09-12 |
| FI864193A0 (fi) | 1986-10-16 |
| EP0220044A2 (en) | 1987-04-29 |
| CN1009092B (zh) | 1990-08-08 |
| GR3001555T3 (en) | 1992-11-23 |
| IL80296A (en) | 1990-06-10 |
| PT83530A (en) | 1986-11-01 |
| NZ217931A (en) | 1989-04-26 |
| EP0220044B1 (en) | 1991-01-30 |
| HUT41769A (en) | 1987-05-28 |
| DK491186A (da) | 1987-04-18 |
| ES2031821T3 (es) | 1993-01-01 |
| DK491186D0 (da) | 1986-10-14 |
| FI864193A7 (fi) | 1987-04-18 |
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